Vercoulen Lab at UMC Utrecht
Unraveling the immune landscape
Spatial omics
Research
Immune dysregulation contributes to diseases such as cancer, chronic inflammation, and immune deficiency. The Vercoulen group develops spatial omics methods to analyze tissues and understand the inflammatory mechanisms that underly these diseases, and response to therapies .
Immune dysregulation and resulting disease can be facilitated by many factors in the tissue. The Vercoulen group aims to unravel the different cell types in the tissue microenvironment, and the crosstalk between cells that contributes to disease and therapy response.
To understand such complex processes, we develop and implement novel and innovative technology: mass cytometry (CyTOF). Mass cytometry allows analysis of single cells, and tissue sections in great detail, to identify cell types, behavior, and their location. We have recently developed a spatial method to analyze single cells in images generated with mass cytometry ‘MATISSE’. We perform spatial omics analysis of proteins, post-translational modifications, and RNA. We highly value our collaborations with fundamental, translational, and clinical colleagues, and strive to develop both innovative tools, generate and share knowledge, drive the field of spatial biology, and impact patient care.
Chronic inflammation and cancer
To study how chronic inflammation contributes to cancer initiation, we are studying a unique cohort of patients with severe inflammatory bowel disease, who are at high risk of developing colorectal cancer. To identify the underlying mechanisms, we apply spatial omics, which allows us to identify relevant cell types and signaling pathways, that localize in and around early cancerous tissue, that are further investigated and targeted in model systems, such as in vitro organoid culture systems. Our long-term aim here is to identify risk factors for cancer development and progress, and eventually molecular targets for safe preventive treatment.
Immune therapy in cancer
Different cancer immune therapy strategies have demonstrated their potency in the clinic, and T cell activation plays a major role in response. We are investigating mechanisms of action of cancer immune therapies, response and toxicity, for checkpoint inhibition therapy, and a novel IgA-based therapy. We study these processes in patient tissue biopsies, and in in vitro culture assays to assess mechanisms of action.
Signal transduction errors
Patients with inborn errors of immunity have defects in their immune system, and suffer from recurrent infections. Counterintuitively, these patients can also suffer from severe autoimmunity with high morbidity. Treating autoimmunity is difficult in these patients, since immune suppression may increase risk of infection. Therefore, we aim to unravel the underlying mechanisms of the disease, by modeling signal transduction upon in vitro receptor stimulation in T cells, and visualizing the inflammatory processes in the tissue affected by autoimmunity.
Tissue heterogeneity: Segmentation and Spatial Analysis
Spatial tissue architectural information is generally ignored by downstream single-cell data analyses. We aim to develop spatial analysis tool for extracting quantitative and comprehensible information on the complex spatial relationships between different cell types and their microenvironments and their organizational features in complex tissues.
Latest updates
Publications
Baars MJD*, Floor E*, Sinha N,*Ter LInde JJM, van Dam S, Amini M, Nijman IJ, ten Hove JR, Drylewicz J, Offerhaus GJA, Laclé MM, Oldenburg B, Vercoulen Y. Multiplex spatial omics reveals changes in immune-epithelial crosstalk during inflammation and dysplasia development in chronic IBD patients iScience, 2024. DOI 10.1016/j.isci.2024.110550Kucukkose E*, Baars MJD*, Amini M, Schraa SJ, Floor E, Bol GM, Borel Rinkes IHM, Roodhart JML, Koopman M, Laoukili J, Kranenburg O, Vercoulen Y. Stromal localization of inactive CD8+ T cells in metastatic mismatch repair deficient colorectal cancer British Journal of Cancer, 2024. DOI 10.1038/s41416-023-02500-xKrijgsman D, Kraaier L, Verdonschot M, Schubert S, Leusen J, Duiker E, de Kleine R, de Meijer V, de Krijger R, Zsiros J, Peng WC, Vercoulen Y. Hepatoblastoma exhibits a predominantly myeloid immune landscape and reveals opportunities for macrophage targeted immunotherapy BioRxiv 2023, DOI: 10.1101/2023.06. 28.546852 Preprint van Eijs M, ter Linde JJM, Baars MJD, Amini M, Lacle MM, Brand EC, Delemarre EM, Drylewicz J, Nierkens S, Verheijden RJ,Oldenburg B, Vercoulen Y, Suijkerbuijk KPM,and van Wijk F. Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor induced colitis iScience, 2023. DOI 10.1016/j.isci.2023.107891van Dam S, Baars MJD, Vercoulen Y. Multiplex Tissue Imaging: Spatial Revelations in the Tumor Microenvironment. Cancers, 2022. DOI: 10.3390/cancers14133170 Krijgsman D*, Sinha N*, Baars MJD*, van Dam S, Amini M, Vercoulen Y. MATISSE: An analysis protocol for combining imaging mass cytometry with fluorescence microscopy to generate single-cell data. STAR Protocols, 2022. DOI: 10.1016/j.xpro.2021.1010Baars MJD, Sinha N, Amini M, Pieterman-Bos A, van Dam S, Ganpat MMP, Laclé MM, Oldenburg B, Vercoulen Y. MATISSE: a method for improved single cell segmentation in imaging mass cytometry. BMC Biology, 2021. DOI: 10.1186/s12915-021-01043-yBakker, D, ter Linde José, Amini M, Ariëns L; van Luijk C, de Bruin-Weller MJD, Thijs J, Vercoulen Y, van Wijk F. Conjunctival inflammation in dupilumab-treated atopic dermatitis comprises a multicellular infiltrate with elevated T1/T17 cytokines: a case series study. Allergy, 2021. DOI: 10.1111/all.15064
Ijssennagger N, van Rooijen K, Magnusdottir S, Ramos Pittol J, Willemsen E; de Zoete M, Baars MJD, Stege P, Colliva C, Pellicciari R, Vercoulen Y, Kuipers F, van Mil S. Liver-gut axis controls the colonic mucus barrier via hepatic FXR. JHEP reports, 2021. DOI: /10.1016/j.jhepr.2021.100344Baars M, Douma T, Simeonov DR, Myers DR, Banerjee S, Kulhanek K, Zwakenberg S, Baltissen MP, De Roock S, van Wijk F, Vermeulen M, Marson A, Roose JP,Vercoulen Y. Dysregulated RasGRP1 expression through RUNX1 mediated transcription promotes autoimmunity. Eur J Immunol, 2021. DOI: 10.1002/eji.201948451Myers DR, Norlin E, Vercoulen Y, Roose JP. Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells. Cell Reports, 2019. DOI: 10.1016/j.celrep.2019.04.037. PMID: 31067469 Vercoulen Y, Kondo Y, Iwig JS, Janssen A, White KA, Amini M, Barber DL, Kuriyan J, Roose JP A histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1. Elife, 2017. DOI: 10.7554/eLife.29002. PMID:28952923.Group members
Yvonne Vercoulen
Principal Investigator — y.vercoulen@umcutrecht.nl
“I am fascinated by immune regulatory mechanisms, with a focus on T cells, from fundamental to clinical. I trained as a PhD, working on Tregs at Utrecht University, and as a postdoc in molecular T cell immunology at UCSF, USA. Now I am Associate Professor & group leader at Center for Molecular Medicine , and scientific director of UCyTOF, UMC Utrecht, and a selected member of Utrecht Young Academy.”
Mojtaba Amini
MSc – technician — m.amini@umcutrecht.nl
“I joined the group of Yvonne Vercoulen in 2017 and I am involved in several research projects in the group. I am manager of the UCyTOF Facility.”
Stephanie van Dam
PhD Candidate
“One of my projects focuses on which immune cell subsets are present in tumors and which subsets can be used for immune response prediction. My other project focuses on unraveling the underlying mechanisms of the primary immune deficiencies, by modeling signal transduction.”
Evelien Floor
PhD Candidate
“ I will study the role of JAK-STAT signaling and JAK inhibitors on tissue cells in chornic inflammation in the gut of patients with inflammatory bowel disease., using spatial proteomics and transcriptomics.”
Iria Lopez Estrada
PhD Candidate
“I started my PhD at the Leusen group (CTI) and Vercoulen lab (CMM). My research will focus on overcoming immunotherapy resistance in colorectal cancer by studying how myeloid immune cells limit treatment effectiveness.”
Faranak Heidari
PhD Candidate
“As part of the TOPGUT MSCA-DN project, I'll be undertaking my PhD at Utrecht University within the team of Dr. Mihaila & Masereeuw and the Vercoulen lab. My research will primarily focus on developing a perfusable chip that replicates both the physiological functions and topographical features of the intestinal lumen. This chip will consist of an epithelial compartment featuring crypt-villi-like patterned hydrogels seeded with intestinal PDOs. My investigation will center on the role of the stroma in supporting tissue maturation and barrier function. Additionally, I'll assess the absorption and biotransformation of various molecules (e.g., bacterial, diet-derived, and drug molecules) from the gut.”
Rhodé van der Kooij
Student —
“I am a Master student in Molecular and Cellular Life Sciences (MCLS) at Utrecht University. During my 9 month internship I want to investigate the mode-of-action of different JAK-STAT inhibitors. I will also be working on setting up a co-culture system to further investigate the interaction between colon eptihelial cells and immune cells. I will be working on this project under the supervision of Evelien Floor."
Kristof van Avondt
Assistant Professor—Spatial Omics Accelerator
“I am coordinating the Spatial Omics Accelerator at the UMCU”
Sofia Frigerio
Visiting PhD Candidate
“I am working on a EU Horizon project to unravel pathogenic mechanisms in IBD (Amsterdam Medical Center), in collaboration with the Vercoulen team (UMCU) to develop and perform spatial tissue analyses.
Former members
Matthijs Baars
PhD candidate
Current: Scientist @Hubrecht Institute
Danielle Krijgsman
Postdoc
Current: Senior scientist @UMC Utrecht
Ian Molendijk
Master Drug Discovery & Innovation UU
Neeraj SInha
Postdoc, in Memoriam
Dorotea Neuberg
Master Science & Business UU
Current: Business Analyst @ Kearney
Meggy Verdonschot
Technician
Current: Technician @VUMC
Iris Langerak
Master Drug Discovery & Innovation UU
Current: CRA @ Julius Clinical
Annelies Pieterman-Bos
MSc Mol. & Cellular Life Sciences UU
Current: PhD candidate @UMCU
Pascalle Hemelop
BSc student & Technician
Current: Research associate @ Genmab
Maroussia Ganpat
Master Cancer Stem cells and Developmental Biology UU
Current: PhD candidate @ Pr. Maxima Center
Aleksandra Makowiezska
Visiting Postdoc
Current: Postdoc @ErasmusMC
Thera Douma
Master Biology of Disease UU
Current : Project leader @ Maag Lever Darm Stichting (gastrointestinal disease foundation)
Sterre van Wierst
Master Cancer Stem Cells & Development
Thijs Demmers
Master Biology of Disease
Positions
If you are interested to join the lab, send an e-mail.
Funding
We are grateful to our funders:
Sacha Swarttouw-Hijmans Stichting. TKI-Health Holland Life Sciences Gastrostrart award (NVGE) KWF Kankerbestrijding
NWO-gravitation program CGC.nl
Strategic Program Cancer-UMCU
WKZ onderzoeksfonds Galapagos BV ISR Bristol Myers Squibb ISR Center for Unusual Collaborations
Contact
Twitter: @VercoulenYvonne
GitHub: VercoulenLab
UCyTOF.nl